Explore the vast range of titles available.

Objectives A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA. Methods Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1. Results Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings. Conclusions These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment, the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the American College of Rheumatology diagnostic criteria in participating centres. We aimed to characterise demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were women. On multivariate analysis, scleroderma subsets (dcSSc vs lcSSc), antibody status and age at onset of Raynaud’s phenomenon, but not gender, were found to be independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis was more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction seemed to be superseded by an antibody-based classification in predicting some scleroderma complications. The EUSTAR MEDS database facilitates the analysis of clinical patterns in SSc, and contributes to the standardised assessment and monitoring of SSc internationally.

Background and purpose: Doxorubicin causes a chronic cardiomyopathy in which reactive oxygen species (ROS) accumulate over time and are associated with genetic and functional lesions of mitochondria. Dexrazoxane is a cardioprotective iron chelator that interferes with ROS production. We aim to analyze the effects of dexrazoxane on mitochondria in the prevention of doxorubicin‐induced chronic myocardial lesions. Experimental approach: Wistar rats (11 weeks of age) were injected with intravenous doxorubicin (0.8 mg kg‐1 weekly for 7 weeks) with or without simultaneous dexrazoxane (8 mg kg‐1). Animals were killed at 48 weeks. Cardiomyopathy was scored clinically and histologically and cardiac mitochondria were analyzed. Key results: Compared to control rats receiving saline, rats treated with doxorubicin alone developed a clinical, macroscopic, histological and ultrastructural cardiomyopathy with low cytochrome c‐oxidase (COX) activity (26% of controls). The expression of the mtDNA‐encoded COX II subunit was reduced (64% of controls). Myocardia exhibited a high production of ROS (malondialdehyde 338% and superoxide 787% of controls). Mitochondria were depleted of mitochondrial DNA (mtDNA copy number 46% of controls) and contained elevated levels of mtDNA deletions. Dexrazoxane co‐administration prevented all these effects of doxorubicin on mitochondria, except that hearts co‐exposed to doxorubicin and dexrazoxane had a slightly lower mtDNA content (81% of controls) and mtDNA deletions at low frequency. Conclusions and Implications: Dexrazoxane prevented doxorubicin induced late‐onset cardiomyopathy and also protected the cardiac mitochondria from acquired ultrastructural, genetic and functional damage. British Journal of Pharmacology (2007) 151, 771–778; doi:10.1038/sj.bjp.0707294

Background A consensus on digital ulcer (DU) definition in systemic sclerosis (SSc) has been recently reached (Suliman et al., J Scleroderma Relat Disord 2:115-20, 2017), while for their evaluation, classification and categorisation, it is still missing. The aims of this study were to identify a set of essential items for digital ulcer (DU) evaluation, to assess if the existing DU classification was useful and feasible in clinical practice and to investigate if the new categorisation was preferred to the simple distinction of DU in recurrent and not recurrent , in patients with systemic sclerosis (SSc). Methods DeSScipher is the largest European multicentre study on SSc. It consists of five observational trials (OTs), and one of them, OT1, is focused on DU management. The DeSScipher OT1 items on DU that reached ≥ 60% of completion rate were administered to EUSTAR (European Scleroderma Trials and Research group) centres via online survey. Questions about feasibility and usefulness of the existing DU classification (DU due to digital pitting scars, to loss of tissue, derived from calcinosis and gangrene) and newly proposed categorisation (episodic, recurrent and chronic) were also asked. Results A total of 84/148 (56.8%) EUSTAR centres completed the questionnaire. DeSScipher items scored by ≥ 70% of the participants as essential and feasible for DU evaluation were the number of DU defined as a loss of tissue (level of agreement 92%), recurrent DU (84%) and number of new DU (74%). For 65% of the centres, the proposed classification of DU was considered useful and feasible in clinical practice. Moreover, 80% of the centres preferred the categorisation of DU in episodic, recurrent and chronic to simple distinction in recurrent/not recurrent DU. Conclusions For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered the proposed classification and categorisation as useful and feasible. The set of items needs to be validated while further implementation of DU classification and categorisation is warranted. Trial registration Observational trial on DU (OT1) is one of the five trials of the DeSScipher project (ClinicalTrials.gov; OT1 Identifier: NCT01836263 , posted on April 19, 2013).

Objective To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). Methods A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores. Results Physicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting. Conclusion The three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.

Background:Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit.Objective:To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients.Methods:A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders.Results:Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, −1.34 (95% CI −1.54 to −1.15) vs −0.93 (95% CI −1.28 to −0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug.Conclusion:This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

We present the second set of discoveries from Keck Observations in the INfrared of Taurus and ρ Oph Exoplanets And Ultracool dwarfs (KOINTREAU), an adaptive optics survey of young stars in the Taurus and ρ Oph star-forming regions using Keck/NIRC2 in conjunction with the Keck infrared pyramid wavefront sensor. We have discovered two faint comoving companions to young stars ISO-Oph 96 and 2MASS J16262785−2625152. The companion to ISO-Oph 96, KOINTREAU-3b, is at a projected separation of 340 au (2 .″ 49). Using our NIRC2 photometry and evolutionary models, and assuming that the companion has the same extinction as its host star, we infer that KOINTREAU-3b has a mass of 3.4 ± 0.7 MJup. The companion to 2MASS J16262785−2625152, KOINTREAU-4b, has a projected separation of 180 au (1 .″ 25) and could have a mass of either 11.5−1.6+1.2 MJup or 15.3−0.8+0.7 MJup, depending on whether the host star is a member of ρ Oph or Upper Sco.

Systemic sclerosis (SSc) is characterised by a progressive microangiopathy that contributes significantly to the morbidity of patients with SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers of endothelial precursor cells (EPCs) might also contribute to the vascular pathogenesis of SSc. However, different protocols for isolation, enrichment, culture and quantification of EPCs are currently used, which complicate comparison and interpretation of the results from different studies.The aim of the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) group expert panel was to provide recommendations for standardisation of future research on EPCs. Consensus statements and recommendations were developed in a face to face meeting by an expert panel of the basic science working group of EUSTAR.The findings were: cardiovascular risk factors and medications such as statins should be described in detail. A detailed description of methods considering isolation, culture, enrichment and detection of EPCs should be given. For in vitro culture of EPCs, no protocol has been shown to be superior to another, but coating with laminin and type IV collagen would resemble most closely the situation in vivo. The endothelial phenotype should be confirmed in all in vitro cultures at the end of the culture period. We recommend using CD133, vascular endothelial growth factor type 2 receptor (VEGFR2) and CD34 in combination with a viability marker for quantification of EPCs in the blood. Finally, exact standard operating procedures for fluorescence-activated cell sorting (FACS) analysis are given that should be strictly followed.In summary, the EUSTAR recommendations will help to unify EPC research and allow better comparison between the results of different studies.

We present the first discoveries from Keck Observations in the Infrared of Taurus and ρ Oph Exoplanets and Ultracool dwarfs (KOINTREAU), an adaptive optics imaging survey of young stars in the Taurus and ρ Oph star-forming regions using the Keck infrared pyramid wavefront sensor. We have found two faint (ΔK∼7 mag), wide-separation companions to two ≈3 Myr old Taurus members. Relative astrometry for these systems shows that both companions are bound to their host stars. We obtained near-infrared spectra of these companions using the Infrared Telescope Facility/SpeX (R ∼100) and the Gemini North InfraRed Spectrograph (Gemini/GNIRS; R ∼ 1000–2000), and combined these with photometry from our NIRC2 imaging, the Pan-STARRS survey, and Spitzer/IRAC archival imaging to constrain their properties. One companion, KOINTREAU-1b (at a projected separation of 690 au), has an average near-infrared spectral type of M9 ± 2, a gravity classification of vl-g, and a changing spectral type between the SpeX (M7) and GNIRS (L1) observations. We estimate this object’s mass to be 10.6−2.3+2.5 MJup, making KOINTREAU-1b the fifth planetary-mass companion found in Taurus. The other companion, KOINTREAU-2b (projected separation 560 au), has a spectral type of M4.5 ± 1 but is ≈4 mag underluminous relative to other Taurus stars of the same spectral type. We detect exceptionally strong He I 1.083 μm emission from this object, indicative of outflows driven by ongoing accretion, but with a conspicuous lack of accompanying H emission. We conclude that KOINTREAU-2b is a young star obscured by an edge-on disk and observed in scattered light. Finally, we derive a distortion solution for NIRC2 imaging, which shows a 0 .° 118 difference in position angle from the previous distortion solution.

Background:Systemic sclerosis (SSc) is a vasculopathy with increased tissue deposition of collagen. The aetiology is unknown. Genetic and environmental susceptibility factors have been implicated. It is unknown whether disease presentation varies within Europe.Aims and Methods:The baseline data of all SSc patients entered in the EULAR Scleroderma Trials and Research (EUSTAR) database up to April 2007 were analysed for geographical differences with regard to organ involvement, and geographical clusters with regard to clinical subsets (diffuse vs limited SSc) and autoantibodies (anticentromere vs anti-Scl70).Results:3661 patients from 79 centres in 62 cities and 23 countries were analysed. There was no clear trend between geographical coordinates and SSc subsets, although there appeared to be an increased prevalence of Scl70 in the more eastern centres. There was no association between geographical longitude or latitude and the age at the onset of Raynaud’s phenomenon or the onset of non-Raynaud’s symptoms. There was also a trend for the more eastern centres to care for patients with a higher prevalence of more severe organ manifestations (pulmonary arterial hypertension, cardiac involvement). Between different centres within one city there was a large variability in the frequency of organ complications.Conclusion:This analysis suggests that eastern centres care for more severe SSc manifestations in Europe. Large differences in patient referral account for a large local variability of SSc presentations and preclude the identification of genetic or environmental factors.